1-Methyl-D-Tryptophan and Docetaxel in Treating Patients With Metastatic Solid Tumors

PRIMARY OBJECTIVES:

I. The MTD of the 1-MT/docetaxel combination using CTCAE 4.0 criteria.

SECONDARY OBJECTIVES:

I. Determination of PK data for the combination of docetaxel plus oral 1-MT.Overall
objective response rate (CR, PR) per RECIST criteria.

OUTLINE: This is a dose-escalation study.

Patients receive oral 1-methyl-d-tryptophan twice daily on days 1-21 and docetaxel IV over 1
hour on day 1 (in course one patients receive 1-methyl-d-tryptophan once daily on days 1 and
3-21). Courses repeat every 21 days in the absence of disease progression or unacceptable
toxicity.

Blood samples are collected periodically for pharmacokinetic and correlative studies.

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed metastatic solid
malignancy

- Preference will be given to patients whose malignancies are treated with
docetaxel as part of routine therapy

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as ≥
20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan

- Patients with known brain metastases will only be eligible after their tumors have
been treated with definitive resection and/or radiotherapy and they are
neurologically stable for at least 1 month off steroids

- ECOG performance status ≤ 2 (Karnofsky ≥ 60%)

- Life expectancy of greater than 4 months

- Leukocytes ≥ 3,000/μL

- Absolute neutrophil count ≥ 1,500/μL

- Platelets ≥ 100,000/μL

- Total bilirubin normal

- AST/ALT ≤ 1.5 times upper limit of normal

- Creatinine normal OR creatinine clearance ≥ 60 mL/min

- Negative pregnancy test

- Not pregnant or nursing

- Sexually active women of child-bearing potential must agree to use two forms of
contraception (hormonal and barrier method of birth control or abstinence) prior to
study entry, for the duration of study participation, and for a minimum of 1 month
after completion of the study; men should be discouraged from fathering children
while on treatment

- No history of gastrointestinal disease causing malabsorption or obstruction such as,
but not limited to, Crohn's disease, celiac sprue, tropical sprue, bacterial
overgrowth/blind loop syndrome, gastric bypass surgery, strictures, adhesions,
achalasia, bowel obstruction, or extensive small bowel resection

- No patients with any active autoimmune disease (i.e., psoriasis, extensive atopic
dermatitis, asthma, IBD, M.S., uveitis, vasculitis), chronic inflammatory condition,
or any condition requiring concurrent use of any systemic immunosuppressants or
steroids for any reason

- Mild-intermittent asthma requiring ONLY occasional beta-agonist inhaler use or
mild localized eczema allowed

- No uncontrolled concurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, myocardial
infarction or percutaneous coronary interventions within the last 6 months, cardiac
arrhythmia, active autoimmune diseases, or major psychiatric illness/social
situations that would limit compliance with study requirements as judged by the
primary investigator at each site

- Patients with well-controlled, chronic medical conditions under the supervision
of the patient's primary physician (i.e., hypertension, hyperlipidemia, coronary
heart disease, diabetes mellitus) are eligible

- No HIV-positive patients or those with other acquired/inherited immunodeficiencies

- No patients with more than one active malignancy at the time of enrollment

- No history of allergic reactions (significant urticaria, angioedema, anaphylaxis)
attributed to compounds of similar chemical or biologic composition to
1-methyl-d-tryptophan (this wouldi nclude L-tryptophan or 5-hydroxy-tryptophan
supplements) or history of severe hypersensitivity reactions to docetaxel or to other
drugs formulated with polysorbate 80

- No patients with an allo-transplant of any kind (this would include those with a
xenograft heart valve)

- No prior treatment with experimental systemic immunotherapies such as CTLA-4 mAb
(with the exception of vaccines)

- No patients who have received any prior experimental active immunotherapy consisting
of targeted monoclonal antibodies or pharmaceutical compounds

- Patients who have received prior experimental vaccine may be enrolled if
approved by the PI

- Patients who have received commercially available active immunotherapies such as
adjuvant interferon must have completed therapy over 1 year prior to enrollment
and have no evidence of autoimmune sequelae

- Prior therapy with approved monoclonal antibodies such as bevacizumab,
cetuximab, panitumumab, or trastuzumab allowed

- No patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier

- Patients may not have received docetaxel in the metastatic setting previously, but
are eligible for the trial if they received docetaxel in the adjuvant setting and at
least one year elapsed between completion of adjuvant chemotherapy and disease
recurrence

- Patients may have received any number of prior chemotherapy treatments

- Patients may not be concomitantly receiving any other investigational agents or
standard therapies with the intent of treating their malignancy while on study

- No supplements containing L-tryptophan or derivatives there of are allowed to be
taken while on study